Diseases of Infancy and Childhood III

Question 1

inborn errors of metabolism

Answer 1

most are autosomal recessive or X-linked

Question 2

PKU

Answer 2

abnormal phenylalanine metabolism

autosomal recessive

PAH mutations
-phenylalanine hydroxylase

untreated - leads to mental retardation and other neuro Sx

Question 3

benign hyperphenylalaninemia

Answer 3

modest elevation in blood phenylalanine

-no associated neuro damage

Question 4

concentration for PKU diagnosis

Answer 4

above 600uM

normal less than 120

Question 5

abnormality in PKU

Answer 5

no phenylalanine to tyrosine

PAH in liver

Question 6

hepatic PAH system

Answer 6

phenylalanine > tyrosine
-PAH

coenzyme - BH4 (tetrahydrobiopterin)

DHPR - converts dihydrobiopterin to replenish BH4

Question 7

lack of PAH

Answer 7

shunt pathways emerge
-increased phenylpyruvic acid, phenyllactic acid, and o-hydroxyphenylacetic acid

large amounts in urine

Question 8

presentation of PKU

Answer 8

musty/mousy odor

severe mental retardation by 6 months

1/3 can’t walk or talk

Question 9

Tx of PKU

Answer 9

diet restriction of phenylalanine

Question 10

maternal PKU

Answer 10

phenylalanine that crosses the placenta and affects fetal organs

**important that maternal dietary restriction occur if she has PKU

Question 11

defects in BH4 recycling

Answer 11

disturb synthesis of neurotransmitters

-neuro defects still present even with normal phenylalanine levels

Question 12

galactosemia

Answer 12

autosomal recessive

disorder of galactose metabolism

Question 13

galactose metabolism

Answer 13

converted to glucose in 3 rxns.

1 - galactose + ATP > galactose-1-P
(galactokinase)

2 - galactose 1-P + UDP-gucose > UDP-galactose + glucose 1-P
(galactose-1-P uridyl transferase)

3 - UDP-galactose > UDP-glucose
(UDP-galactose 4 epimerase)

Question 14

GALT

Answer 14

enzyme for rxn 2
-galactose-1-P uridyl transferase

more common**

Question 15

galactokinase

Answer 15

enzyme for rxn 1

rare deficiency**

Question 16

path of galactosemia

Answer 16

galactose 1-P accumulates in liver, spleen, lens, kidneys, heart, cerebral cortex, erythrocytes

Question 17

presentation of galactosemia

Answer 17

cataracts
hepatomegaly (fatty liver)
alterations in CNS

also jaundice, aminoaciduria

Question 18

infection of galactosemia

Answer 18

E. coli

Question 19

diagnosis of galactosemia

Answer 19

presence of reducing sugar other than glucose in the urine

more reliable - testing presence of GALT

Question 20

Tx of galactosemia

Answer 20

removal of galactose from diet

-for first 2 years of life

Question 21

cystic fibrosis

Answer 21

autosomal recessive

disorder of ion transport in epithelial cells
-effects exocrine glands and epithelium of resp, GI, and repro tracts

Question 22

presentation of cystic fibrosis

Answer 22

chronic lung disease
pancreatic insufficiency
steatorrhea
malnutrition
hepatic cirrhosis
intestine obstruction
male infertility

Question 23

most common lethal genetic disease affecting caucasians

Answer 23

cystic fibrosis

Question 24

defect in CF

Answer 24

cystic fibrosis transmembrane conductance regulator
-CFTR

regulator of multiple ion channels - specifically ENaC

Question 25

ENaC

Answer 25

normally inhibitied by CFTR

except in sweat glands - stimulates

Question 26

loss of CFTR in sweat glands

Answer 26

decreased ENaC activity

• increased Na and Cl in lumen of sweat duct
• salty tasting sweat

Question 27

loss of CFTR in airway and GI

Answer 27

increased Na back into cell
decreased Cl out of cell
-increased water into cell

dehydrated mucus as a result

Question 28

path of CF

Answer 28

isotonic but low volume surface fluid layer in resp and GI tracts

Question 29

CFTR and bicarb

Answer 29

mediates transport

-results in release of acidic fluids

Question 30

classes of mutations in CF

Answer 30

6 total

1, 2, 3, are severe - class CF
4, 5  are mild

Question 31

class I CF

Answer 31

defective protein synthesis of CFTR

Question 32

class II CF

Answer 32

abnormal protein folding, processing, trafficking

-no CFTR at apical surface

Question 33

class III CF

Answer 33

defective regulation of CFTR - no ATP binding

nonfunctional CFTR at apical surface

Question 34

class IV CF

Answer 34

decreased conductance
-mutation in transmembrane domain (chloride ion pore)

milder phenotype

Question 35

class V CF

Answer 35

reduced abundance
-reduced amount of normal protein

milder phenotype

Question 36

class VI CF

Answer 36

altered regulation of separate ion channels

Question 37

class CF

Answer 37

pancreatic insufficiency
sinopulmonary infection
GI symtoms

Question 38

MBL2 and TGFB1

Answer 38

alter severity of CF manifestations

Question 39

infection with CF

Answer 39

pseudomonas aeruginosa

-colonize lower resp tract

Question 40

alginate

Answer 40

produced in lungs of CF patient
-hypoxic environment favors this

forms biofilm that protects bacteria from antibodies and antibiotics

Question 41

bronchiectasis

Answer 41

with CF

-thickened airways with fibrosis

Question 42

meconeum ileus

Answer 42

with CF

-thickened and obstructed bowel

Question 43

azoospermia

Answer 43

mild forms of CF

-maybe no vas deferens

Question 44

pancreatic changes in CF

Answer 44

atrophy of exocrine glands
fibrosis
squamous metaplasia
dilation of ducts

Question 45

most serious complications of CF

Answer 45

pulmonary changes

-secondary obstruction and increased infections

Question 46

3 common infections in lung for CF

Answer 46

staph aureus
hemophilus influenzae
pseudomonas aeruginosa

Question 47

burkholderia cepacia

Answer 47

infection in CF

• not good
• cepacia syndrome
• longer hospital stays
• increased mortalilty

Question 48

causes of death in CF

Answer 48

lung infections, obstructive lung disease, cor pulmonale

Question 49

diagnosis of CF

Answer 49

sequencing of CFTR gene